Pediatric Crohn Disease Medication

The goals of pharmacotherapy in Crohn disease are to reduce morbidity and prevent complications. Agent classes used include 5-aminosalicylic acid (5-ASA) derivatives, corticosteroids, immunosuppressive agents, biologic agents, and antibiotics.

Class Summary

5-ASA derivatives are used to treat mild-to-moderate Crohn disease and to maintain remission.

Mesalamine (Asacol, Pentasa, Rowasa, Canasa)

Mesalamine inhibits leukotriene biosynthesis via the lipoxygenase pathway of arachidonic acid metabolism and interferes with myeloperoxidase activity and reactive oxygen species. The oral mesalamine products currently approved in the United States differ only with respect to the mechanism of drug delivery. Mesalamine is approved by the US Food and Drug Administration (FDA) for treatment of UC but is widely used off label for treatment of Crohn disease.

Mesalamine products have not been approved for use in children but are considered standard of care for inflammatory bowel disease (IBD) and are supported by numerous reports in the literature.

Asacol contains mesalamine within a Eudragit-S coating that dissolves and releases the mesalamine at pH 7, which typically occurs in the terminal ileum. Pentasa contains 5-ASA in ethylcellulose and has a time-release coating. Release of mesalamine from Pentasa begins at the pylorus; consequently, this drug is often used when proximal intestinal Crohn disease is suggested. Despite the drug's proximal release site, there are no convincing data to indicate that the site of release translates into clinical superiority.

Rectal dosage forms deliver high concentrations of mesalamine to the left colon as high as the splenic flexure (enema with 30 minutes retention) or to the rectum for use in proctitis (suppository). Although mesalamine is effective, it is associated with a relatively high relapse rate upon discontinuance. In many cases, widespread use of topical agents is limited by patient acceptance; often, patients with active rectal disease have difficulty holding in the enema.

Class Summary

Corticosteroids are used to treat active moderate-to-severe disease. They are not indicated for maintenance therapy. Budesonide is available in ileal controlled-release form and is used for the treatment of ileal or right-side colonic disease.

Prednisone

Prednisone exercises its anti-inflammatory effects through decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Methylprednisolone (Medrol, Solu-Medrol)

Methylprednisolone exerts its anti-inflammatory effects by means of decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Budesonide (Entocort EC)

Budesonide exerts its anti-inflammatory effects by means of decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Hydrocortisone (Cortenema, Anusol-HC, Anucort HC, Anu-med HC, Proctosol-HC)

Hydrocortisone is a rectally administered corticosteroid similar to the intravenous (IV) and oral corticosteroids; significant amounts of corticosteroids can be absorbed systemically when these agents are administered via an enema or suppository. Various products containing hydrocortisone are available for rectal use. This agent is useful for treating distal colonic disease.

Class Summary

Immunosuppressive agents are used to treat moderate-to-severe Crohn disease, to treat steroid-dependent or steroid-refractory disease, and to maintain remission.

6-Mercaptopurine (Purinethol)

6-Mercaptopurine (6-MP) and its prodrug, azathioprine, are purine analogues that interfere with protein synthesis and nucleic acid metabolism. 6-MP has a cytotoxic effect on lymphoid cells. The onset of action is delayed for 2-3 months.

Azathioprine (Imuran, Azasan)

Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease the proliferation of immune cells, which lowers autoimmune activity.

Methotrexate (Trexall, Rheumatrex)

Methotrexate impairs DNA synthesis, induces apoptosis, and reduces production of interleukin (IL)-1. It is used for treatment of moderate-to-severe disease and maintenance of remission. The onset of action is delayed.

Class Summary

Biologic agents are used in the treatment of active Crohn disease or fistulizing disease that is unresponsive to other medical therapy.

Infliximab (Remicade)

Infliximab is a chimeric immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that neutralizes cytokine tumor necrosis factor (TNF)-α and inhibits its binding to TNF-α receptors. It reduces infiltration of inflammatory cells and TNF-α production in inflamed areas.

Adalimumab (Humira)

Adalimumab is a recombinant human IgG1 monoclonal antibody that is specific for human TNF. It binds specifically to TNF-α and blocks interaction with p55 and p75 cell-surface TNF receptors.

Class Summary

Antibiotics are used in the treatment of mild-to-moderate Crohn disease, fistulizing disease, and perianal disease. They may change the microbial flora of the intestine and have a potential effect on the cell-mediated immune system.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa.

Ciprofloxacin (Cipro)

Ciprofloxacin inhibits bacterial DNA synthesis and, consequently, growth.